Multi-centre, prospective randomized comparison of three different substrate ablation strategies for persistent atrial fibrillation.

AIMS: The optimal strategy for persistent atrial fibrillation (PerAF) is poorly defined. We conducted a multicentre, randomized, prospective trial to compare the outcomes of different ablation strategies for PerAF. METHODS AND RESULTS: We enrolled 450 patients and randomly assigned them in a 1:1:1 ratio to undergo pulmonary vein isolation and subsequently undergo the following three different ablation strategies: anatomical guided ablation (ANAT group, n = 150), electrogram guided ablation (EGM group, n = 150), and extensive electro-anatomical guided ablation (EXT group, n = 150). The primary endpoint was freedom from atrial fibrillation (AF) lasting longer than 30 s at 12 months after a single ablation procedure. After 12 months of follow-up, 72% (108) of patients in the EXT group were free from AF recurrence, as compared with the 64% (96) in the EGM group (P = 0.116), and 54% (81) in the ANAT group (P = 0.002). The EXT group showed less AF/atrial tachycardia recurrence than the EGM group (60% vs. 50%, P = 0.064) and the ANAT group (60% vs. 37.3%, P < 0.001). The EXT group showed the highest rate of AF termination (66.7%), followed by 56.7% in the EGM group, and 20.7% in the ANAT group. The AF termination signified less AF recurrence at 12 months compared to patients without AF termination (30.1% vs. 42.7%, P = 0.008). Safety endpoints did not differ significantly between the three groups (P = 0.924). CONCLUSIONS: Electro-anatomical guided ablation achieved the most favourable outcomes among the three ablation strategies. The AF termination is a reliable ablation endpoint.

Electrogram dispersion-guided driver ablation adjunctive to high-quality pulmonary vein isolation in atrial fibrillation of varying durations.

OBJECTIVE: To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression. METHODS: A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping. RESULTS: The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001). CONCLUSION: The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.

The cardiac autonomic nervous system: A target for modulation of atrial fibrillation.

The cardiac autonomic nerve system (CANS) is a potentially potent modulator of the initiation and perpetuation of atrial fibrillation (AF). In this review, we focus on the relationship between the autonomic nervous system (ANS) and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia from eight aspects. We conclude that Activation and Remodeling of CANS involved in the initiation and maintenance of AF. The network control mechanism, innervation regions, and sympathetic/parasympathetic balance play an important role in AF substrate. And the formation of Complex Fractional Atrial Electrograms also related to CANS activity. In addition, modulating CANS function by potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, and low-level vagal nerve stimulation, may enable AF to be controlled. Although the role of the ANS has long been recognized, a better understanding of the complex interrelationships of the various components of the CANS will lead to improvement of treatments for this common arrhythmia.

Regulation of Atrial Fibrosis by the Bone.

MR (mineralocorticoid receptor) antagonists have been demonstrated to provide beneficial effects on preventing atrial fibrosis. However, the underlying cellular and molecular mechanisms remain unclear. We aim to determine the role of osteoblast MR in atrial fibrosis and to explore the underlying mechanism. Using osteoblast MR knockout mouse in combination with mutant TGF (transforming growth factor)-ß1 transgenic mouse, we demonstrated that MR deficiency in osteoblasts significantly attenuated atrial fibrosis. Mechanistically, MR directly regulated expression of OCN (osteocalcin) in osteoblasts. Both carboxylated and undercarboxylated OCNs (ucOC) were less secreted in osteoblast MR knockout mice. Mutant TGF-ß1 transgenic mice supplemented with recombinant ucOC showed aggravated atrial fibrosis. In cultured atrial fibroblasts, ucOC treatment promoted proliferation and migration of atrial fibroblasts, whereas cotreatment with an antagonist for a GPRC6A (G-protein-coupled receptor, family C, group 6, member A) abolished these effects. Western blotting analysis revealed upregulation of PKA (protein kinase A) and CREB (cAMP-response element-binding protein) phosphorylation after ucOC treatment. Inhibition of PKA with its antagonist reduced ucOC-induced proliferation and migration of atrial fibroblasts. Finally, the impact of osteoblast MR deficiency on atrial fibrosis was abolished by ucOC administration in mutant TGF-ß1 transgenic mice. Taken together, MR deficiency in osteoblasts attenuated atrial fibrosis by downregulation of OCN to promote proliferation and migration of atrial fibroblasts.

Extra pulmonary vein driver mapping and ablation in paroxysmal atrial fibrillation by electrogram dispersion analysis.

BACKGROUND: The adjunctive approach is still unknown for atrial fibrillation (AF), which cannot be terminated after pulmonary vein isolation (PVI). We hypothesized that the driver ablation plus PVI was superior to PVI alone. METHODS AND RESULTS: A total of 98 patients with paroxysmal AF were enrolled in this study and were divided into two groups, with one group undergoing PVI (n = 49) and the other group undergoing PVI + driver ablation (n = 49). The driver regions were defined as clusters of bipolar electrograms that displayed spatial dispersion spread over mean AF cycle length at a minimum of three adjacent bipolars of a PentaRay catheter. During the procedure, the most prominent driver regions before PVI were the roof (n = 27; 55.1%), PV antrum (n = 23; 46.9%), and the inferoposterior wall (n = 11; 22.4%). PVI can eliminate all drivers at PV antrum, but only terminate 30.4% of AF in the driver group. The AF termination rate in the driver ablation group was significantly higher than that in conventional ablation (93.9% vs 40.6%; P < 0.001). The rate of freedom from atrial tachyarrhythmia episodes by a single procedure at 6 months was significantly higher in the driver group than in the conventional group (91.6% vs 72.4%; P = 0.02). CONCLUSION: The present method is effective for AF driver identification. It guided ablation adjunctive to PVI increasing the rate of AF termination and improving the outcomes in patients with paroxysmal AF.

Atrial Substrate Modification in Atrial Fibrillation: Targeting GP or CFAE? Evidence from Meta-Analysis of Clinical Trials.

Several clinically relevant outcomes post atrial substrate modification in patients with atrial fibrillation (AF) have not been systematically analyzed among published studies on adjunctive cardiac ganglionated plexi (GP) or complex fractionated atrial electograms (CFAE) ablation vs. pulmonary vein isolation (PVI) alone. Out of 176 reports identified, the present meta-analysis included 14 randomized and non-randomized controlled trials (1613 patients) meeting inclusion criteria. Addition of GP ablation to PVI significantly increased freedom from atrial tachyarrhythmia in short- (OR: 1.72; P = 0.003) and long-term (OR: 2.0, P = 0.0006) follow-up, while adjunctive CFAE ablation did not after one or repeat procedure (P<0.05). The percentage of atrial tachycardia or atrial flutter (AT/AFL) after one procedure was higher for CFAE than GP ablation. In sub-analysis of non-paroxysmal AF, relative to PVI alone, adjunctive GP but not CFAE ablation significantly increased sinus rhythm maintenance (OR: 1.88, P = 0.01; and OR:1.24, P = 0.18, respectively). Meta regression analysis of the 14 studies indicated that sample size was significant source of heterogeneity either in outcomes after one or repeat procedure. In conclusion, in patients with AF, adjunctive GP but not CFAE ablation appeared to significantly add to the beneficial effects on sinus rhythm maintenance of PVI ablation alone; and CFAE ablation was associated with higher incidence of subsequent AT/AFL.

Effects of endothelin-1 chronic stimulation on electrical restitution, beat-to-beat variability of repolarization, and ventricular arrhythmogenesis.

Chronically elevated levels of endothelin-1 (ET-1) have been detected in several cardiovascular diseases. In this study, we investigated the chronic effects of ET-1 on the electrophysiological characteristics expected to influence the genesis and maintenance of ventricular arrhythmia (VA). Rabbits were randomized to ET-1 (ET-1 group) or 0.9% saline (control group) for 2 weeks. The S1-S2 protocol and S1-S1 dynamic pacing were performed to assess the action potential duration restitution (APDR) and to induce APD alternans or VA in 4 sites of Langendorff-perfused rabbit hearts. The beat-to-beat variability of repolarization was quantified as short-term variability and long-term variability. Compared with the control group, chronic ET-1 administration significantly prolonged QT intervals, APD at 90% repolarization (APD90), and effective refractory period (ERP), steepened the maximum slopes of the APDR curve, decreased the ERP/APD90 ratio, and increased the spatial dispersions of APD90, ERP, and maximum slopes (P < 0.05 for all). Moreover, chronic ET-1 administration markedly increased the short-term variability and long-term variability (P < 0.01 for all). APD alternans occurred in both groups, but the threshold of APD alternans was decreased at all sites in the ET-1 group (P < 0.01 for all). We also observed that chronic ET-1 stimulation significantly increased the incidence and duration of the VA episodes. These results suggest that chronic stimulation with ET-1 facilitated VA by steepening the APDR curve and increasing the spatial dispersion of APDR and beat-to-beat variability of repolarization.

Cardiac electrophysiological differences between Kunming and C57BL6/J mice.

OBJECTIVE: To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming (KM) and C57BL6/J (C57) mice. METHODS: Electrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration (APD) in conventional and programmed electrical stimulation (PES). Transient outward potassium current (Ito) was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes. RESULTS: QT interval was prolonged in KM mice relative to C57 mice (62.51±4.47 ms vs. 52.59±4.85 ms, P<0.05) The APD at 50% repolarization of the left ventricular epicardium (18.60±0.91 ms vs. 12.90±0.35 ms), and APDs at 50% (17.31±6.05 ms vs. 12.00±3.24 ms) and 70% repolarization (36.13±5.32 ms vs. 21.95±8.06 ms) of the right ventricular epicardium in KM mice were more sensitive to PES-induced ventricular tachycardia (25%, 3 of 12 hearts), and especially to Burst-induced ventricular tachycardia (50%, 6 of 12 hearts)compared with C57 mice, which were 20% (2 of 10 hearts) and 30% (3 of 10 hearts) respectively. Ito densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively (all P<0.01). CONCLUSION: Our data showed that KM mice with the prolonged QT interval and APD are vulnerabilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes obtained from KM mice than that from C57 mice.

Controlled study on therapeutic effect of vessel pricking therapy and western medication for treatment of Henoch-Schonlein purpura nephritis / 中国针灸

<p><b>OBJECTIVE</b>To compare the difference of therapeutic effects between vessel pricking therapy and Prednisone for treatment of Henoch-Schonlein purpura nephritis.</p><p><b>METHODS</b>Seventy cases of acute purpura nephritis syndrome were randomly divided into an observation group (40 cases) and a control group (30 cases). Patients in observation group were differentiated into sthenia and asthenia syndromes. Vessel pricking therapy was applied at Hegu (LI 4), Quchi (LI 11), Xuehai (SP 10) etc. by triangular needle for sthenia symptom; shallow needling was used at Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36) etc. by filiform needle. The control group was treated with oral admi-nidtration of Prednisone. The symptom score of TCM, 24 h urinary protein, red blood cell count of urinary sediment of both groups were observed before and after treatment and therapeutic effects were compared.</p><p><b>RESULTS</b>The total effective rate of 92.5% (37/40) in observation group was superior to that of 80.0% (24/30) in control group, and there was a significant difference between two groups (P < 0.05); the symptom score of TCM, 24 h urinary protein, red blood cell count of urinary sediment were all improved in both groups after treatment (all P < 0.05), and moreover, the improvement in observation group was superior to that of control group (all P < 0.05); after treatment, the symptom score of TCM of sthenia syndrome was lower than that of asthenia syndrome in observation group (P < 0.05).</p><p><b>CONCLUSION</b>Vessel pricking therapy has a significant therapeutic effect for treatment of Henoch-Schonlein purpura nephritis, superior to that of oral administration of Prednisone, and the therapeutic effect is better for treating sthenia syndrome than for asthenia syndrome.</p>